Immune checkpoint blockade in oncology:Many types of cancer cells evolve mechanisms to evade control and elimination by the immune system. Such mechanisms can include inhibition of so-called 'immune checkpoints', which would normally be involved in the maintenance of immune homeostasis. An increasingly important area of clinical oncology research is the development of new agents which impede these evasion techniques, thereby switching immune vigilance back on, and effecting immune destruction of cancer cells. Three molecular targets of checkpoint inhibitors which are being extensively pursued are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). Using antibody-based therapies targeting these pathways, clinical responses have been reported in various tumour types, including melanoma, renal cell carcinoma [10] and non-small cell lung cancer [6,9].

Pembrolizumab was the first-in-class, anti-PD-1 antibody to be approved by the US FDA, followed in quick succession by nivolumab. Additional anti-PD-1 mAbs are in various stages of clinical development; e.g. BCD-100 (Biocad; Phase 2/3 melanoma and NSCLC), PDR001 (Novartis; Phase 1-3 in various advanced malignancies, being evaluated in many combination studies with other agents), IBI308 (Innovent Biologics; most advanced study is Phase 3 in advanced or metastatic NSCLC), and SHR-1210 (Jiangsu HengRui Medicine Co; most advanced trials are Phase 3 studies for non-squamous NSCLC and esophageal carcinoma).

Synthetic small-molecule PD-1 inhibitors are in development e.g. Curis' CA-170 which is an orally active PD-1/VISTA antagonist in Phase 1 clinical trial (NCT02812875) in patients with advanced solid tumours and lymphomas.

Immune checkpoint blockade in Alzheimer's disease (AD): In mouse models of AD anti-PD-1 antibody treatment was used to induce immune checkpoint blockade. The biological response included an interferon (IFN)-γ-dependent systemic immune response and recruitment of monocyte-derived macrophages to the brain, which was associated with amyloid β plaque clearance and improved cognitive function. These results point to immune checkpoints as valid targets for therapeutic intervention in AD [2].

PD-1 as a new drug target for asthma:Yu et al. (2016) [11] have identified high PD-1 expression in a population of innate lymphoid cell (ILC) progenitors and activated ILC2 cells. Antibody-induced depletion of PD-1 ILCs reduces cytokine levels in inflammation models, including reducing lung inflammation in a papain-induced asthma model. The authors suggest this may represent an alternative pathway for development of novel immunotherapies for immune disease prevention and control.

In mouse models of Alzheimer's disease anti-PD1 antibody treatment was used to induce immune checkpoint blockade. The biological response included an interferon (IFN)-γ-dependent systemic immune and recruitment of monocyte-derived macrophages to the brain, which was associated amyloid beta plaque clearance and improved cognitive function. These results point to immune checkpoints as valid targets for therapeutic intervention in Alzheimer's disease.